Intranasal delivery of therapeutic enzymes to the central nervous system for the treatment of lysosomal storage diseases

Abstract

The invention provides a method to prevent, inhibit or treat one or more neurological symptoms associated with a lysosomal storage disease in a mammal in need thereof, which includes intranasally administering to the mammal a composition comprising an effective amount of a lysosomal storage enzyme or a recombinant adeno-associated virus vector comprising an open reading frame encoding a lysosomal storage enzyme. Also provided are compositions and devices useful in the methods.

What is claimed is: 
     
       1. A method for treating or inhibiting one or more neurological signs or symptoms associated with a mucopolysaccharidosis in a mammal in need thereof, comprising:
 intranasally administering an effective amount of an enzyme composition comprising alpha-L-iduronidase, iduronate-2-sulfatase, N-acetyl-alpha-D-glucosaminidase, betagalactosidase, or beta-glucuronidase. 
 
     
     
       2. The method of  claim 1  wherein the administration inhibits neurological degeneration. 
     
     
       3. The method of  claim 1  wherein the enzyme is alpha-L-iduronidase. 
     
     
       4. The method of  claim 1  wherein the mammal is a human. 
     
     
       5. The method of  claim 1  wherein the mucopolysaccharidosis is related to a deficiency in alpha-L-iduronidase. 
     
     
       6. The method of  claim 1  wherein the mucopolysaccharidosis is a mucopolysaccharide type I disorder, a mucopolysaccharidosis type II disorder, or a mucopolysaccharidosis type VII disorder. 
     
     
       7. The method of  claim 1  wherein multiple doses are administered. 
     
     
       8. The method of  claim 1  wherein the composition is administered weekly. 
     
     
       9. The method of  claim 1  wherein the composition is administered daily. 
     
     
       10. The method of  claim 1  wherein the pH of the composition is about 4 to about 9. 
     
     
       11. The method of  claim 1  wherein the pH of the composition is about 5 to about 7. 
     
     
       12. The method of  claim 1  wherein about 200 to about 400 μL of the composition is administered. 
     
     
       13. The method of  claim 1  wherein the concentration of the enzyme in the composition is about 5 mg/mL to about 25 mg/mL. 
     
     
       14. The method of  claim 1  wherein about 1 to about 7 mg of the enzyme is administered. 
     
     
       15. The method of  claim 1  wherein the administration treats neurological degeneration. 
     
     
       16. The method of  claim 1  wherein the composition is administered to the upper one third of the nasal cavity. 
     
     
       17. The method of  claim 1  wherein the composition does not include a permeation enhancer.